The goal of this laboratory is to understand the molecular basis of insulin action. Both biochemical and morphological approaches are used, with the former being supported by this grant. Cell types used will be adipocytes, hepatocytes, and various cultured cell types. The following objectives are to be pursued: 1. Studies on insulin second messenger. These will focus on trying to learn how the messenger is made by the membrane, to completely characterize and identify the material and to determine how it acts on the various insulin-sensitive enzyme systems, through alteration of phosphorylation and calcium. 2. To study insulin binding and what role disulfide bonds play in insulin binding with membranes from various cell types and in the initiation of insulin's action. 3. To begin studies to identify the 120,000 molecular weight phosphoprotein of the plasma membrane from rat adipocytes that is sensitive to the direct addition of insulin. This phosphoprotein could be part of the insulin receptor itself or could be the calcium pump ATPase of the plasma membrane.